Updated results of a phase I, open-label study of BCMA/CD19 dual-targeting fast CAR-T GC012F for patients with relapsed/refractory multiple myeloma (RRMM).
Authors: Juan Du, Wei-Jun Fu, Hua Jiang, Baoxia Dong, Li Gao, Li Liu, Jian Ge, Aili He, Lu Li, Jing Lu, Xiequn Chen, Jia Liu, Qi Zhang, Jiaping He, Lianjun Shen, Lihong Weng, Hua Zhang, Wei Cao, Wenling Li
Journal: Journal of Clinical Oncology (2023)

8005 Background: GC012F is a chimeric antigen receptor (CAR)-T cell therapy with B cell maturation antigen (BCMA) and CD19 dual-target developed on the novel FasT CAR-T platform enabling 22-36 h manufacturing. Our previous results were presented at ASCO and EHA 2022 for 29 pts (NCT04236011; NCT04182581), which demonstrated GC012F treatment led to deep and durable response in RRMM pts. Furthermore, initial results showed that GC012F showed considerable efficacy and safety in high-risk transplant-eligible newly diagnosed MM pts (Blood 2022; 140 (Supplement 1): 889–890). Here we present update on RRMM study with a longer median follow-up. Methods: From October 2019 to January 2022, 29 heavily pretreated RRMM pts (age 27-76) with a median of 5 prior lines therapies (range 2-9) received GC012F. 26 (89.7%) pts were high risk (HR- mSMART), 8 (27.6%) pts had EM disease, 24 (82.8%) pts were refractory to last therapy. 10 (34.5%) pts had received prior anti-CD38 and 11 (37.9%) pts were treated with auto-HSCT. After lymphodepletion over 2-3 days (30 mg/m 2 /d, 300mg/m 2 /d Flu/Cy), GC012F was administered as single infusion at 3 dose levels: 1x10 5 /kg (DL1) n=2, 2x10 5 /kg (DL2) n=10 and 3x10 5 /kg (DL3) n=17. Results: At the time of data cut-off (January 30, 2023), 29 eligible pts had been evaluated for response with the last patient completed 12 months efficacy follow up. Overall response rate was 93.1% (27/29), stringent complete response rate was 82.8% (24/29), ≥very good partial response rate was 89.7% (26/29). All patients dosed (29/29) achieved MRD negativity by flow cytometry (sensitivity 10 -4 -10 -6 ). To date 24/29 patients (82.8%) achieved MRD- sCR across all dose levels. According to the Kaplan-Meier method, the median duration of response (DOR) was 37.0 months (95%CI, 11.0-NR) and the median progression free survival (PFS) was 38.0 months (95%CI, 11.8-NR). Cytokine Release Syndrome (CRS) was reported in 25 (86.2%) pts, which was mostly ≤grade 2 (n=23, 79.3%) and 2 (6.9%) pts were grade 3. No ICANS was observed (Graded by ASBMT criteria). Median duration of CRS was 3 days (1-8 d). PK results showed no difference amongst dose levels DL1 to DL3. The median time of persistence was 410 days (range: 51-1183) and GC012F was still detectable in 23 (79.3%) pts at 6 months and in 16 (55.2%) pts at 12 months after infusion. sBCMA plasma levels started declining at day 4 in 80% (8/10) patients, falling sharply at day 10 in 100% (19/19), and reaching minimal levels from 30 to 60 days post infusion in 100% (29/29) patients. Conclusions: The updated results showed GC012F continues to provide deep and durable responses, and a very high MRD negativity ratein RRMM pts, including in pts refractory to anti-CD38, PIs and IMIDs. Based on these promising results of the study of GC012F for RRMM, further clinical studies will be conducted to confirm the efficacy of GC012F. Clinical trial information: NCT04236011 ; NCT04182581 .